A5069824138- Pancreatic function and diabetes
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Diabetes Management and Research
- Adipose Tissue and Metabolism
- Dietary Effects on Health
- Cholesterol and Lipid Metabolism
- Cancer, Hypoxia, and Metabolism
- GDF15 and Related Biomarkers
- Erythrocyte Function and Pathophysiology
- Diet, Metabolism, and Disease
- Nutrition and Health in Aging
- Long-Term Effects of COVID-19
- Dermatological and COVID-19 studies
- COVID-19 Clinical Research Studies
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Neuroendocrine Tumor Research Advances
- Poxvirus research and outbreaks
- Bacillus and Francisella bacterial research
- MicroRNA in disease regulation
- Herpesvirus Infections and Treatments
- Neuropeptides and Animal Physiology
- Drug Transport and Resistance Mechanisms
University Hospital of Geneva
2010-2024
University of Geneva
2007-2021
Geneva College
2013
Hôpital Beau-Séjour
2011
Inserm
2004-2005
Université Claude Bernard Lyon 1
2004
The Pax6 transcription factor is crucial for endocrine cell differentiation and function. Indeed, mutations of are associated with a diabetic phenotype drastic decrease insulin-positive number. Our aim was to better define the β-cell transcriptional network thus provide further information concerning role in We developed Pax6-deficient model rat primary β-cells specific small interfering RNA leading 75% knockdown expression. Through candidate gene approach, we confirmed that controls mRNA...
The sterol regulatory element binding protein 1 (SREBP-1) is regarded as a major factor involved in the nutritional regulation of lipogenesis. aim present work was to demonstrate its involvement response key genes glucose and lipid metabolism liver, adipose tissue, skeletal muscle during fasting refeeding. hexokinase-2 (HKII) investigated marker metabolic pathway that FAS lipogenic pathway. vivo association SREBP-1 with promoter regions these determined different tissues using chromatin...
The paired box homeodomain Pax6 is crucial for endocrine cell development and function plays an essential role in glucose homeostasis. Indeed, mutations of are associated with diabetic phenotype. Importantly, homozygous mutant mice characterized by markedly decreased β δ cells absent α cells. To better understand the critical that exerts glucagon-producing cells, we developed a model primary rat study transcriptional network adult differentiated generated Pax6-deficient using either specific...
Clinical and experimental data indicate a beneficial effect of estrogens on energy glucose homeostasis associated with improved insulin sensitivity positive effects secretion. The aim the study was to investigate impact proglucagon-producing cells, pancreatic α enteroendocrine L cells. consequences sexual hormone deprivation were evaluated in ovariectomized mice (ovx). Ovx exhibited impaired tolerance during oral tests (OGTT), which decreased GLP-1 intestinal secretion content, an that...
Abstract Background The global mpox outbreak which started in May 2022 was caused by a novel clade IIb variant of the virus (MPXV). It differed from traditional Western and Central Africa disease transmission patterns clinical presentation. Methods To address need for detailed virologic data, we conducted an observational cohort study (MOSAIC) during 2022-July 2023 individuals with confirmed MPXV infection enrolled six European Countries. Case-management decisions were left to attending...
The Forkhead box A transcription factors are major regulators of glucose homeostasis. They show both distinct and redundant roles during pancreas development in adult mouse β-cells. In vivo ablation studies have revealed critical implications Foxa1 on glucagon biosynthesis requirement Foxa2 α-cell terminal differentiation. order to examine the respective role these mature α-cells, we used small interfering RNA (siRNA) directed against rat primary pancreatic α-cells rodent lines leading...
Glucose homeostasis depends on the coordinated secretion of glucagon, insulin, and Glucagon-like peptide (GLP)-1 by pancreas intestine. Obesity, which is associated with an increased risk developing insulin resistance type 2 diabetes, affects function these organs. Here, we investigate functional molecular adaptations proglucagon-producing cells in obese mice to better define their involvement diabetes development. We used GLU-Venus transgenic male specifically expressing Venus fluorochrome...
Specific expression of the glucagon gene in rat pancreas requires presence G1 element localized at -100/-49 base pairs on promoter. Although it is known that multiple transcription factors such as Pax-6, Cdx-2/3, c-Maf, Maf-B, and Brain-4 can activate promoter through G1, their relative importance vivo unknown. We first studied Cdx-2/3 developing adult mouse pancreas. Maf-B was detectable a progressively increasing number alpha-cells throughout development adulthood, c-Maf were expressed low...
Insulin upregulates hexokinase II (HKII) expression in skeletal muscle, and this effect is altered type 2 diabetic patients. This study was conducted to identify the transcription factors that mediate of insulin on HKII gene human muscle. We have cloned promoter region investigated its regulation a primary culture muscle cells. defined (−369/−270) conferred transcriptional response insulin. contains sterol regulatory element (SRE) interacted with recombinant active form SRE binding...
The transcription factor Nkx6.1 is required for the establishment of functional insulin-producing β-cells in endocrine pancreas. Overexpression has been shown to inhibit glucagon gene expression while favouring insulin activation. Down-regulation resulted opposite effect, suggesting that absence favours expression. To understand mechanism by which suppresses expression, we studied its effect on promoter activity non-islet cells using transient transfections and gel-shift analyses. In...
Pax6 is important in the development of pancreas and was previously shown to regulate pancreatic endocrine differentiation, as well insulin, glucagon, somatostatin genes. Prohormone convertase 2 (PC2) main processing enzyme alpha cells, where it processes proglucagon produce glucagon under spatial temporal control 7B2, which functions a molecular chaperone. To investigate role biosynthesis, we studied potential target genes InR1G9 cells transfected with small interfering RNA clones...
The Pax6 transcription factor is crucial for pancreatic α-cells. Indeed, Pax6-deficient mouse models are characterized by markedly altered α-cell differentiation. Our objective was to investigate the role of in glucagon secretion process. We used a model rat primary enriched-α cells with specific small interfering RNA leading 70% knockdown expression. first showed that decreases biosynthesis as well release. Through physiological assays, we demonstrated decrease affects specifically acute...
Diabetes is a complex disease implicating several organs and cell types. Within the islets, dysregulation occurs in both alpha- beta-cells, leading to defects of insulin secretion increased glucagon secretion. Dysregulation alpha-cells associated with transcriptome changes. We hypothesized that microRNAs (miRNAs) which are negative regulators mRNA stability translation could be involved alpha-cell alterations or adaptations during type 2 diabetes. miRNA microarray analyses were performed on...
Abstract Glucagon and α-cell dysfunction are critical in the development of hyperglycemia during diabetes both humans rodents. We hypothesized that leading to dysregulated glucagon secretion is due a lack insulin intrinsic defects. To characterize diabetes, we used glucagon-Venus transgenic male mice induced insulinopenic by streptozotocin administration alterations secretion. investigated vivo impact on glucagon-producing cells using FACS-sorted α-cells from control diabetic mice....
Characterization of endocrine-cell functions and associated molecular signatures in diabetes is crucial to better understand why by which mechanisms alpha beta cells cause perpetuate metabolic abnormalities. The now recognized role glucagon control a major incentive have understanding dysfunctional cells. To characterize alterations diabetes, we analyzed alpha-cell transcriptome from diabetic mice using diet-induced obesity model. this aim, quantified the expression levels total mRNAs sorted...
Pancreatic beta cell dysfunction is a hallmark of type 2 diabetes. Growth differentiation factor 15 (GDF15), which an energy homeostasis regulator, has been shown to improve several metabolic parameters in the context However, its effects on pancreatic beta-cell remain be identified. We, therefore, performed experiments using models and histological sectioning wild-type knock-out GDF15 mice determine effect insulin secretion viability. A bioinformatics analysis was identify GDF15-correlated...
Circadian clocks have been developed in evolution as an anticipatory mechanism allowing for adaptation to the constantly changing light environment due rotation of Earth. This is functional all light-sensitive organisms. There a considerable body evidence on tight connection between circadian clock and most aspects physiology metabolism. Clocks, operative pancreatic islets, caught particular attention last years recent reports their critical roles regulation insulin secretion etiology type 2...
Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding the role glucagon-like peptide-1 (GLP-1) physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation obesity evaluated regulation miRNAs through microarray analyses on sorted from control obese glucose-intolerant (I-HFD) hyperglycemic (H-HFD) mice after 16 weeks respectively low-fat diet (LFD) or high-fat (HFD) feeding. The identified altered...
SARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) a well-established, widely available vasoactive and angioprotective drug interacting with sulphate, the potential interfere uptake of by epithelial cells. The CADOVID trial aims evaluate efficacy safety CaD in reducing viral load non-hospitalised adult patients diagnosed COVID-19, confirmed positive PCR, including reduce impact...
Beta cell failure is one of the most important features type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) has been proposed to improve β-cell function. However, mechanisms involved in this process are still poorly understood. The aim study was investigate contribution sphingosine-1-phosphate (S1P) impact HDL treatment on insulin secretion by pancreatic β-cells and determine its mechanisms. Primary cultures isolated from rat were treated with or without presence absence S1P...